A Study of Perjeta (Pertuzumab) in Combination With Herceptin (Trastuzumab) and Chemotherapy in Patients With HER2-Positive Metastatic Gastroesophageal Junction or Gastric Cancer - Full Text View

Purpose

This double-blind, placebo-controlled, randomized, multicenter, international, parallel arm study will evaluate the efficacy and safety of Perjeta (pertuzumab) in combination with Herceptin (trastuzumab), fluoropyrimidine and cisplatin as first-line treatment in patients with HER2-positive metastatic gastroesophageal junction or gastric cancer. Patients will be randomized to receive Perjeta 840 mg or placebo intravenously (iv) every 3 weeks in combination with Herceptin (initial dose of 8 mg/kg iv followed by 6 mg/kg iv every 3 weeks) and cisplatin and fluoropyrimidine (capecitabine or 5-fluorouracil) for the first 6 treatment cycles. Patients will continue to receive Perjeta or placebo and Herceptin until disease progression or unacceptable toxicity occurs.

Condition	Intervention	Phase
Gastric Cancer	Drug: pertuzumab [Perjeta] Drug: placebo Drug: trastuzumab [Herceptin] Drug: cisplatin Drug: capecitabine Drug: 5-fluorouracil	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED, MULTICENTER PHASE III STUDY EVALUATING THE EFFICACY AND SAFETY OF PERTUZUMAB IN COMBINATION WITH TRASTUZUMAB AND CHEMOTHERAPY IN PATIENTS WITH HER2-POSITIVE METASTATIC GASTROESOPHAGEAL JUNCTION OR GASTRIC CANCER

Resource links provided by NLM:

MedlinePlus related topics: Cancer Stomach Cancer

Drug Information available for: Fluorouracil Cisplatin Capecitabine Trastuzumab Pertuzumab

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Overall survival: Time from randomization to death of any cause [ Time Frame: approximately 4.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival: Time from randomization to first occurrence of disease progression, as determined by the investigator according to RECIST v1.1 criteria, or death of any cause [ Time Frame: approximately 4.5 years ] [ Designated as safety issue: No ]
Overall objective response (partial response + complete response) occurring on two consecutive occasions >/= 4 weeks apart, as determined by the investigator according to RECIST v1.1 criteria [ Time Frame: approximately 4.5 years ] [ Designated as safety issue: No ]
Duration of objective response: Time from occurrence of objective response to progressive disease, as determined by investigator according to RECIST v1.1 criteria, or death of any cause [ Time Frame: approximately 4.5 years ] [ Designated as safety issue: No ]
Clinical benefit rate: Best response of complete response or partial response or stable disease for 6 weeks or longer, as determined by the investigator according to RECIST v1.1 criteria [ Time Frame: approximately 4.5 years ] [ Designated as safety issue: No ]
Safety: Incidence of adverse events [ Time Frame: approximately 4.5 years ] [ Designated as safety issue: No ]
Safety: Incidence of left ventricular systolic dysfunction (symptomatic or asymptomatic) [ Time Frame: approximately 4.5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	780
Study Start Date:	April 2013
Estimated Study Completion Date:	June 2015
Estimated Primary Completion Date:	June 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Pertuzumab + TFP	Drug: pertuzumab [Perjeta] 840 mg iv every 3 weeks Drug: trastuzumab [Herceptin] 8 mg/kg iv initial dose on Day 1, followed by 6 mg/kg iv every 3 weeks Drug: cisplatin 80 mg/m2 iv every 3 weeks, 6 cycles Drug: capecitabine 1000 mg/m2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) every 3 weeks, 6 cycles (or 5-fluorouracil) Drug: 5-fluorouracil 800 mg/m2/24 hours iv by continuous infusion for 120 hours (Days 1-5) every 3 weeks, 6 cycles (or capecitabine)
Placebo Comparator: Placebo + TFP	Drug: placebo pertuzumab placebo iv every 3 weeks Drug: trastuzumab [Herceptin] 8 mg/kg iv initial dose on Day 1, followed by 6 mg/kg iv every 3 weeks Drug: cisplatin 80 mg/m2 iv every 3 weeks, 6 cycles Drug: capecitabine 1000 mg/m2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) every 3 weeks, 6 cycles (or 5-fluorouracil) Drug: 5-fluorouracil 800 mg/m2/24 hours iv by continuous infusion for 120 hours (Days 1-5) every 3 weeks, 6 cycles (or capecitabine)

Arms

Assigned Interventions

Experimental: Pertuzumab + TFP

Drug: pertuzumab [Perjeta]

840 mg iv every 3 weeks

Drug: trastuzumab [Herceptin]

8 mg/kg iv initial dose on Day 1, followed by 6 mg/kg iv every 3 weeks

Drug: cisplatin

80 mg/m2 iv every 3 weeks, 6 cycles

Drug: capecitabine

1000 mg/m2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) every 3 weeks, 6 cycles (or 5-fluorouracil)

Drug: 5-fluorouracil

800 mg/m2/24 hours iv by continuous infusion for 120 hours (Days 1-5) every 3 weeks, 6 cycles (or capecitabine)

Placebo Comparator: Placebo + TFP

Drug: placebo

pertuzumab placebo iv every 3 weeks

Drug: trastuzumab [Herceptin]

8 mg/kg iv initial dose on Day 1, followed by 6 mg/kg iv every 3 weeks

Drug: cisplatin

80 mg/m2 iv every 3 weeks, 6 cycles

Drug: capecitabine

1000 mg/m2 orally twice daily, evening of Day 1 to morning of Day 15 (28 doses) every 3 weeks, 6 cycles (or 5-fluorouracil)

Drug: 5-fluorouracil

800 mg/m2/24 hours iv by continuous infusion for 120 hours (Days 1-5) every 3 weeks, 6 cycles (or capecitabine)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult patients, >/= 18 years of age
HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction
Measurable or evaluable non-measurable disease as assessed by the investigator according to RECIST v1.1 criteria
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Life expectancy >/= 3 months

Exclusion Criteria:

Previous cyctotoxic chemotherapy for advanced (metastatic) disease
Evidence of disease progression documented within 6 months after completion of prior neoadjuvant or adjuvant cytotoxic chemotherapy, or both, or radiotherapy for GEJ adenocarcinoma
Previous treatment with any HER2-directed therapy, at any time, for any duration
Previous exposure to any investigational treatment within 30 days before the first dose of study treatment
Radiotherapy within 30 days before the first dose of study treatment (within 2 weeks if given as palliation to peripheral bone metastases, if recovered from all toxicities)
History or evidence of brain metastases
Clinically significant active GI bleeding (Grade >/= 2 according to NIC-CTCAEv.4.03)
Other malignancy (in addition to GC) within 5 years before enrollment, except for carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin that has been previously treated with curative intent
Inadequate hematologic, renal or liver function
Pregnant or lactating women
History of congestive heart failure of any New York Heart Association (NYHA) criteria
Angina pectoris requiring treatment
Myocardial infarction within the past 6 months before the first dose of study drug
Clinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmia
History or evidence of poorly controlled hypertension
Baseline left ventricular ejection fraction (LVEF) value < 55%
Any significant uncontrolled intercurrent systemic illness
Positive for hepatitis B, hepatitis C or HIV infection

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01774786

Contacts

Contact: Please reference Study ID Number: BO25114 www.roche.com/about_roche/roche_worldwide.htm

888-662-6728 (U.S. Only)

genentechclinicaltrials@druginfo.com

Show 135 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01774786 History of Changes
Other Study ID Numbers:	BO25114
Study First Received:	January 21, 2013
Last Updated:	May 13, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Trastuzumab
Capecitabine
Cisplatin

Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on May 23, 2013